CDK9 Inhibitor Induces the Apoptosis of B-Cell Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolytic Metabolism

B-cell acute lymphocytic leukemia (B-ALL), a common blood cancer in children, leads to high mortality. Cyclin-dependent kinase 9 inhibitor (CDK9i) effectively attenuates acute myeloid leukemia and chronic lymphoblastic leukemia by inducing apoptosis and inhibiting cell proliferation. However, the ef...

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Published inFrontiers in cell and developmental biology Vol. 9; p. 641271
Main Authors Huang, Wen-Li, Abudureheman, Tuersunayi, Xia, Jing, Chu, Lei, Zhou, Hang, Zheng, Wei-Wei, Zhou, Neng, Shi, Rong-Yi, Li, Ming-Hao, Zhu, Jian-Min, Qing, Kai, Ji, Chao, Liang, Kai-Wei, Guo, Sa, Yin, Gang, Duan, Cai-Wen
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 04.03.2021
Subjects
B-cell acute lymphocytic leukemia
c-Myc
CDK9 inhibitors
Cell and Developmental Biology
cell apoptosis
glycolysis
cell apoptosis
CDK9 inhibitors
c-Myc
B-cell acute lymphocytic leukemia
glycolysis
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Summary:B-cell acute lymphocytic leukemia (B-ALL), a common blood cancer in children, leads to high mortality. Cyclin-dependent kinase 9 inhibitor (CDK9i) effectively attenuates acute myeloid leukemia and chronic lymphoblastic leukemia by inducing apoptosis and inhibiting cell proliferation. However, the effect of CDK9i on B-ALL cells and the underlying mechanisms remain unclear. In this study, we showed that CDK9i induced the apoptosis of B-ALL cells by activating the apoptotic pathways. In addition, CDK9i restrained the glycolytic metabolism of B-ALL cells, and CDK9i-induced apoptosis was enhanced by co-treatment with glycolysis inhibitors. Furthermore, CDK9i restained the glycolysis of B-ALL cell lines by markedly downregulating the expression of glucose transporter type 1 (GLUT1) and the key rate-limiting enzymes of glycolysis, such as hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA). Moreover, cell apoptosis was rescued in B-ALL cells with over-expressed c-Myc after treatment with CDK9i, which is involved in the enhancement of glycolytic metabolism. In summary, our findings suggest that CDK9 inhibitors induce the apoptosis of B-ALL cells by inhibiting c-Myc-mediated glycolytic metabolism, thus providing a new strategy for the treatment of B-ALL.
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Edited by: Meng Zhao, Sun Yat-sen University, China
These authors have contributed equally to this work
Reviewed by: Jun Fan, Jinan University, China; Weiping Yuan, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China; Qifa Liu, Southern Medical University, China; Pengxu Qian, Zhejiang University, China
This article was submitted to Signaling, a section of the journal Frontiers in Cell and Developmental Biology
ISSN:2296-634X
2296-634X
DOI:10.3389/fcell.2021.641271